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Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease

The microtubule-associated protein Tau (MAPT) is a major component of the pathogenesis of a wide variety of brain-damaging disorders, known as tauopathies. These include Alzheimer's disease (AD), denoted as secondary tauopathy because of the obligatory combination with amyloid pathology. In all...

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Autores principales: Crespo-Biel, Natalia, Theunis, Clara, Van Leuven, Fred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376502/
https://www.ncbi.nlm.nih.gov/pubmed/22720188
http://dx.doi.org/10.1155/2012/251426
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author Crespo-Biel, Natalia
Theunis, Clara
Van Leuven, Fred
author_facet Crespo-Biel, Natalia
Theunis, Clara
Van Leuven, Fred
author_sort Crespo-Biel, Natalia
collection PubMed
description The microtubule-associated protein Tau (MAPT) is a major component of the pathogenesis of a wide variety of brain-damaging disorders, known as tauopathies. These include Alzheimer's disease (AD), denoted as secondary tauopathy because of the obligatory combination with amyloid pathology. In all tauopathies, protein Tau becomes aberrantly phosphorylated, adopts abnormal conformations, and aggregates into fibrils that eventually accumulate as threads in neuropil and as tangles in soma. The argyrophilic neurofibrillary threads and tangles, together denoted as NFT, provide the postmortem pathological diagnosis for all tauopathies. In AD, neurofibrillary threads and tangles (NFTs) are codiagnostic with amyloid depositions but their separated and combined contributions to clinical symptoms remain elusive. Importantly, NFTs are now considered a late event and not directly responsible for early synaptic dysfunctions. Conversely, the biochemical and pathological timeline is not exactly known in human tauopathy, but experimental models point to smaller Tau-aggregates, termed oligomers or multimers, as synaptotoxic in early stages. The challenge is to molecularly define these Tau-isoforms that cause early cognitive and synaptic impairments. Here, we discuss relevant studies and data obtained in our mono- and bigenic validated preclinical models, with the perspective of Tau as a therapeutic target.
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spelling pubmed-33765022012-06-20 Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease Crespo-Biel, Natalia Theunis, Clara Van Leuven, Fred Int J Alzheimers Dis Review Article The microtubule-associated protein Tau (MAPT) is a major component of the pathogenesis of a wide variety of brain-damaging disorders, known as tauopathies. These include Alzheimer's disease (AD), denoted as secondary tauopathy because of the obligatory combination with amyloid pathology. In all tauopathies, protein Tau becomes aberrantly phosphorylated, adopts abnormal conformations, and aggregates into fibrils that eventually accumulate as threads in neuropil and as tangles in soma. The argyrophilic neurofibrillary threads and tangles, together denoted as NFT, provide the postmortem pathological diagnosis for all tauopathies. In AD, neurofibrillary threads and tangles (NFTs) are codiagnostic with amyloid depositions but their separated and combined contributions to clinical symptoms remain elusive. Importantly, NFTs are now considered a late event and not directly responsible for early synaptic dysfunctions. Conversely, the biochemical and pathological timeline is not exactly known in human tauopathy, but experimental models point to smaller Tau-aggregates, termed oligomers or multimers, as synaptotoxic in early stages. The challenge is to molecularly define these Tau-isoforms that cause early cognitive and synaptic impairments. Here, we discuss relevant studies and data obtained in our mono- and bigenic validated preclinical models, with the perspective of Tau as a therapeutic target. Hindawi Publishing Corporation 2012 2012-06-08 /pmc/articles/PMC3376502/ /pubmed/22720188 http://dx.doi.org/10.1155/2012/251426 Text en Copyright © 2012 Natalia Crespo-Biel et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Crespo-Biel, Natalia
Theunis, Clara
Van Leuven, Fred
Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title_full Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title_fullStr Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title_full_unstemmed Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title_short Protein Tau: Prime Cause of Synaptic and Neuronal Degeneration in Alzheimer's Disease
title_sort protein tau: prime cause of synaptic and neuronal degeneration in alzheimer's disease
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376502/
https://www.ncbi.nlm.nih.gov/pubmed/22720188
http://dx.doi.org/10.1155/2012/251426
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